Olanzapine's effects on hypothalamic transcriptomics and kinase activity

Sandra Pereira; Laura N Castellani; Chantel Kowalchuk; Khaled Alganem; Xiaolu Zhang; William G Ryan; Raghunath Singh; Sally Wu; Emily Au; Roshanak Asgariroozbehani; Sri Mahavir Agarwal; Adria Giacca; Robert E Mccullumsmith; Margaret K Hahn

doi:10.1016/j.psyneuen.2024.106987

Olanzapine's effects on hypothalamic transcriptomics and kinase activity

Psychoneuroendocrinology. 2024 May:163:106987. doi: 10.1016/j.psyneuen.2024.106987. Epub 2024 Feb 6.

Authors

Affiliations

¹ Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
² Centre for Addiction and Mental Health, Toronto, ON, Canada.
³ Department of Neurosciences, University of Toledo, Toledo, OH, USA.
⁴ Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
⁵ Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
⁶ Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada.
⁷ Centre for Addiction and Mental Health, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting & Best Diabetes Centre, Toronto, ON, Canada.
⁸ Department of Physiology, University of Toronto, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Banting & Best Diabetes Centre, Toronto, ON, Canada.
⁹ Department of Neurosciences, University of Toledo, Toledo, OH, USA; ProMedica, Neuroscience Institute, Toledo, OH, USA.
¹⁰ Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Pharmacology, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada; Banting & Best Diabetes Centre, Toronto, ON, Canada. Electronic address: margaret.hahn@camh.ca.

PMID: 38340539
PMCID: PMC10947847 (available on 2025-05-01)
DOI: 10.1016/j.psyneuen.2024.106987

Abstract

Olanzapine is a second-generation antipsychotic that disrupts metabolism and is associated with an increased risk of type 2 diabetes. The hypothalamus is a key region in the control of whole-body metabolic homeostasis. The objective of the current study was to determine how acute peripheral olanzapine administration affects transcription and serine/threonine kinase activity in the hypothalamus. Hypothalamus samples from rats were collected following the pancreatic euglycemic clamp, thereby allowing us to study endpoints under steady state conditions for plasma glucose and insulin. Olanzapine stimulated pathways associated with inflammation, but diminished pathways associated with the capacity to combat endoplasmic reticulum stress and G protein-coupled receptor activity. These pathways represent potential targets to reduce the incidence of type 2 diabetes in patients taking antipsychotics.

Keywords: Kinome array; Olanzapine; RNA-seq.

MeSH terms

Animals
Antipsychotic Agents* / metabolism
Antipsychotic Agents* / pharmacology
Benzodiazepines / metabolism
Benzodiazepines / pharmacology
Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / metabolism
Gene Expression Profiling
Humans
Hypothalamus / metabolism
Olanzapine / metabolism
Olanzapine / pharmacology
Rats

Substances

Olanzapine
Benzodiazepines
Antipsychotic Agents

Abstract

MeSH terms

Substances

Grants and funding